Stem Cell Clinic

A 5th person is likely cured of HIV, and another is in long-term remission – NBC News

Two new cases presented Wednesday at the International AIDS Conference in Montreal have advanced the field of HIV cure science, demonstrating yet again that ridding the body of all copies of viable virus is indeed possible, and that prompting lasting viral remission also might be attainable.

In one case, scientists reported that a 66-year-old American man with HIV has possibly been cured of the virus through a stem cell transplant to treat blood cancer. The approach which has demonstrated success or apparent success in four other cases uses stem cells from a donor with a specific rare genetic abnormality that gives rise to immune cells naturally resistant to the virus.

In another case, Spanish researchers determined that a woman who received an immune-boosting regimen in 2006 is in a state of what they characterize as viral remission, meaning she still harbors viable HIV but her immune system has controlled the viruss replication for over 15 years.

Experts stress, however, that it is not ethical to attempt to cure HIV through a stem cell transplant a highly toxic and potentially fatal treatment in anyone who is not already facing a potentially fatal blood cancer or other health condition that would make them a candidate for such a treatment.

While a transplant is not an option for most people with HIV, these cases are still interesting, still inspiring and illuminate the search for a cure, Dr. Sharon Lewin, an infectious disease specialist at the Peter Doherty Institute for Infection and Immunity at the University of Melbourne, told reporters on a call last week ahead of the conference.

There are also no guarantees of success through the stem cell transplant method. Researchers have failed to cure HIV using this approach in a slew of other people with the virus.

Nor is it clear that the immune-enhancing approach used in the Spanish patient will work in additional people with HIV. The scientists involved in that case told NBC News that much more research is needed to understand why the therapy appears to have worked so well in the woman it failed in all participants in the clinical trial but her and how to identify others in whom it might have a similar impact. They are trying to determine, for example, if specific facets of her genetics might favor a viral remission from the treatment and whether they could identify such a genetic profile in other people.

The ultimate goal of the HIV cure research field is to develop safe, effective, tolerable and, importantly, scalable therapies that could be made available to wide swaths of the global HIV population of some 38 million people. Experts in the field tend to think in terms of decades rather than years when hoping to achieve such a goal against a foe as complex as this virus.

Diagnosed with HIV in 1988, the man who received the stem cell transplant is both the oldest person to date 63 years old at the time of the treatment and the one living with HIV for the longest to achieve an apparent success from a stem cell transplant cure treatment.

The white male dubbed the City of Hope patient after the Los Angeles cancer center where he received his transplant 3years ago has been off of antiretroviral treatment for HIV for 17 months.

We monitored him very closely, and to date we cannot find any evidence of HIV replicating in his system, said Dr. Jana Dickter, an associate clinical professor in the Division of Infectious Diseases at City of Hope. Dickter is on the patients treatment team and presented his case at this weeks conference.

This means the man has experienced no viral rebound. And even through ultra-sensitive tests, including biopsies of the mans intestines, researchers couldnt find any signs of viable virus.

The man was at one time diagnosed with AIDS, meaning his immune system was critically suppressed. After taking some of the early antiretroviral therapies, such as AZT, that were once prescribed as individual agents and failed to treat HIV effectively, the man started a highly effective combination antiretroviral treatment in the 1990s.

In 2018, the man was diagnosed with acute myeloid leukemia, or AML. Even when HIV is well treated, people with the virus are still at greater risk of a host of cancers that are associated with aging, including AML and other blood cancers. Thanks to effective HIV treatment, the population of people living with the virus in the U.S. is steadily aging; the majority of people diagnosed with HIV is now older than 50.

He was treated with chemotherapy to send his leukemia into remission prior to his transplant. Because of his older age, he received a reduced intensity chemotherapy to prepare him for his stem cell transplant a modified therapy that older people with blood cancers are better able to tolerate and that reduces the potential for transplant-related complications.

Next, the man received the stem cell transplant from the donor with an HIV-resistant genetic abnormality. This abnormality is seen largely among people with northern European ancestry, occurring at a rate of about 1% among those native to the region.

According to Dr. Joseph Alvarnas, a City of Hope hematologist and a co-author of the report, the new immune system from the donor gradually overtook the old one a typical phenomenon.

Some two years after the stem cell transplant, the man and his physicians decided to interrupt his antiretroviral treatment. He has remained apparently viable-virus free ever since. Nevertheless, the study authors intend to monitor him for longer and to conduct further tests before they are ready to declare that he is definitely cured.

A second report presented at the Montreal conference detailed the case of a 59-year-old woman in Spain who is considered to be in a state of viral remission.

The woman was enrolled in a clinical trial in Barcelona in 2006 of people receiving standard antiretroviral treatment. She was randomized to also receive 11 months of four therapies meant to prime the immune system to better fight the virus, according to Nria Climent, a biologist at the University of Barcelona Hospital Clinic, who presented the findings.

Then Climent and the research team decided to take the woman off her antiretrovirals, per the studys planned protocol. She has now maintained a fully suppressed viral load for over 15 years. Unlike the handful of people either cured or possibly cured by stem cell transplants, however, she still harbors virus that is capable of producing viable new copies of itself.

Her body has actually controlled the virus more efficiently with the passing years, according to Dr. Juan Ambrosioni, an HIV physician in the Barcelona clinic.

Ambrosioni, Climent and their collaborators said they waited so long to present this womans case because it wasnt until more recently that technological advances have allowed them to peer deeply into her immune system and determine how it is controlling HIV on its own.

Its great to have such a gaze, Ambrosioni said, noting that the point is to understand what is going on and to see if this can be replicated in other people.

In particular, it appears that what are known as her memory-like NK cells and CD8 gamma-delta T cells are leading this effective immunological army.

The research team noted that they do not believe that the woman would have controlled HIV on her own without the immune-boosting treatment, because the mechanisms by which her immune cells appear to control HIV are different from those seen in elite controllers, the approximately 1 in 200 people with HIV whose immune systems can greatly suppress the virus without treatment.

Lewin, of Australias Peter Doherty Institute, told reporters last week that it is still difficult to judge whether the immune-boosting treatment the woman received actually caused her state of remission. Much more research is needed to answer that question and to determine if others might also benefit from the therapy she received, she said.

Over four decades, just five people have been cured or possibly cured of HIV.

The virus remains so vexingly difficult to cure because shortly after entering the body it infects types of long-lived immune cells that enter a resting, or latent, state. Because antiretroviral treatment only attacks HIV when infected cells are actively churning out new viral copies, these resting cells, which are known collectively as the viral reservoir and can stay latent for years, remain under the radar of standard treatment. These cells can return to an active state at any time. So if antiretrovirals are interrupted, they can quickly repopulate the body with virus.

The first person cured of HIV was the American Timothy Ray Brown, who, like the City of Hope patient, was diagnosed with AML. His case was announced in 2008 and then published in 2009. Two subsequent cases were announced at a conference in 2019, known as the Dsseldorf and London patients, who had AML and Hodgkin lymphoma, respectively. The London patient, Adam Castillejo, went public in 2020.

Compared with the City of Hope patient, Brown nearly died after the two rounds of full-dose chemotherapy and the full-body radiation he received. Both he and Castillejo had a devastating inflammatory reaction to their treatment called graft-versus-host disease.

Dr. Bjrn Jensen, of Dsseldorf University Hospital, the author of the German case study one typically overlooked by HIV cure researchers and in media reports about cure science said that with 44 months passed since his patient has been viral rebound-free and off of antiretrovirals, the man is almost definitely cured.

We are very confident there will be no rebound of HIV in the future, said Jensen, who noted that he is in the process of getting the case study published in a peer-reviewed journal.

For the first time, University of Cambridges Ravindra Gupta, the author of the London case studystated, in an email to NBC News, that with nearly five years passed since Castillejo has been off of HIV treatment with no viral rebound, he is definitely cured.

In February, a research team announced the first case of a woman and the first in a person of mixed race possibly being cured of the virus through a stem cell transplant. The case of this woman, who had leukemia and is known as the New York patient, represented a substantial advance in the HIV cure field because she was treated with a cutting-edge technique that uses an additional transplant of umbilical cord blood prior to providing the transplant of adult stem cells.

The combination of the two transplants, the study authors told NBC News in February, helps compensate for both the adult and infant donors being less of a close genetic match with the recipient. Whats more, the infant donor pool is much easier than the adult pool to scan for the key HIV-resistance genetic abnormality. These factors, the authors of the womans case study said, likely expand the potential number of people with HIV who would qualify for this treatment to about 50 per year

Asked about the New York patients health status, Dr. Koen van Besien, of the stem cell transplant program at Weill Cornell Medicine and New York-Presbyterian in New York City, said, She continues to do well without detectable HIV.

Over the past two years, investigators have announced the cases of two women who are elite controllers of HIV and who have vanquished the virus entirely through natural immunity. They are considered likely cured.

Scientists have also reported several cases over the past decade of people who began antiretroviral treatment very soon after contracting HIV and after later discontinuing the medications have remained in a state of viral remission for years without experiencing viral rebound.

Speaking of the reaction of the City of Hope patient, who prefers to remain anonymous, to his new HIV status, Dickter said: Hes thrilled. Hes really excited to be in that situation where he doesnt have to take these medications. This has just been life-changing.

The man has lived through several dramatically different eras of the HIV epidemic, she noted.

In the early days of HIV, he saw many of his friends and loved ones get sick and ultimately die from the disease, Dickter said. He also experienced so much stigma at that time.

As for her own feelings about the case, Dickter said, As an infectious disease doctor, Id always hoped to be able to tell my HIV patients that theres no evidence of virus remaining in their system.

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A 5th person is likely cured of HIV, and another is in long-term remission - NBC News

A new era: After winding path and safety scares, gene therapy enters the clinic – Sydney Morning Herald

What weve dreamed about for several decades now is becoming reality, says Professor Ian Alexander, head of the gene therapy research unit at the Childrens Medical Research Institute. We are about to see a big rush of these therapies coming into the clinic. Its really started screaming upwards in the last few years its exponential.

We stand on the very tip of the iceberg. The first gene therapy was approved in China in 2004; over the next 10 years, global regulators approved just four more. In just the past 18 months, regulators have approved five treatments with two more awaiting final approval and another 3633 therapies in the pipeline, according to tracking by the American Society of Gene and Cell Therapy.

Were at the stage where there is a huge bulge coming down the clinical trial pipeline. Its almost exceeding capacity, says Dr Thomas Edwards, head of retinal gene therapy research at the Centre for Eye Research Australia. Its an exciting time for patients, it wasnt long ago we had nothing for them.

Many of the drugs we have, such as penicillin or Tamiflu, work by killing bacteria or viruses. Vaccination uses a dead virus to prime the immune system. Synthetic hormones like insulin treat the bodys own shortages. Chemicals in pill form, such as selective serotonin reuptake inhibitors, float through the bloodstream, enter our cells and change our chemistry.

Gene therapy is different. Rather than alter our chemistry, it treats us by changing our genotype, the way our DNA is expressed.

It is a new paradigm. It offers the first possibility of curing diseases at their root genetic cause and the possibility of a lifelong cure, says Rasko. And we are seeing that now in patients.

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Understanding Zolgensma gives you an idea of how different this new medical era will be.

Every time you go to scroll an article or turn the page in a newspaper, your brain converts that thought to a signal. It runs down your spinal cord to motor neurons, cells that reside in the cord but project thin tendrils out into the flesh. These tendrils called axons carry commands from neuron to muscle.

Like every cell in your body, each motor neuron carries a full copy of your genome, separated across 23 pairs of chromosomes and locked tight in the cells nucleus.

On chromosome five is a short stretch of genetic code known as SMN1. This gene is a blueprint for a protein crucial to the motor neurons function.

SMN1 is in an unfortunate place. The stretch of chromosome it lies in is prone to errors. Make a coding error in SMN1 and you blur the blueprint. The motor neurons struggle to build their crucial protein and soon start dying.

Without motor neurons, the signals from the brain to eat, to move, even to breathe stop getting through. In about 1 in every 10,000 babies born in Australia every year, this gene has an error.

Zolgensma, marketed by Novartis, comes in a small syringe, just 50 milliltres. Inside the syringe, in fluid, is a genetically-modified adeno-associated virus, the organic machines that make the treatment possible.

As far as science can tell, AAVs are harmless to humans. They infect us without us ever knowing. Scientists slice out the part of the viruss genetic code and replace it with a copy of SMN1. Inside the body, it crosses from the blood to the spinal cord and quickly infects motor neuron cells. Its the perfect vehicle, says Associate Professor Michelle Farrar, a paediatric neurologist who led a clinical trial of the drug at Sydney Childrens Hospitals Network.

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The virus enters the nucleus the vault where DNA is kept and releases its copy of the SMN1 gene. Unlike Gattaca-style genetic editing, the new gene is not incorporated into the patients DNA but floats nearby. Extra genetic code attached to the gene instructs the cell to activate it and start churning out copies of the key protein the motor neurons need.

Unlike most cells in the body, motor neurons dont divide; youre born with all you have. This is why losing them is so dangerous but it also means that if you can repair the faulty gene, you should have a therapy that works long-term. Some patients are now eight years post-treatment with no sign its wearing off, says Farrar.

Zolgensma does come with risks: serious liver injury or failure. Two patients on one of the drugs key clinical trials had signs of liver damage; a third had swelling on the brain requiring surgery.

Indeed, liver damage remains a problem with many gene treatments, with multiple deaths reported in clinical trials.

It remains unclear why. But the therapies rely on treating one disease by essentially infecting a patient with a benign virus, and when you put something in the blood a lot of it is going to end filtered out by the liver. One theory: in some people the immune system might spot and attack the build-up of virus in the liver, leading to extreme systemic inflammation and death.

Safety concerns have dogged gene therapy ever since the death of Jesse Gelsinger the young man who, in 1999, became the face of the treatments limitations after he died while participating in a clinical trial.

His death was a very sobering experience for the field, says Alexander from the Childrens Medical Research Institute a sign that scientists understood far less than they thought. There was a mismatch between the technology and the understanding.

Rasko is tougher on his colleagues. In 1999, when Jesse passed, essentially the whole field stunk. Everyone was accused of overhyping, and no one was delivering.

In response, the field curtailed its ambition and pivoted toward diseases that are a better match for the quickly developing technology.

Early treatments were held up because of the struggle to deliver enough of the gene without provoking a huge immune response. By switching to adeno-associated viruses small viruses that infect humans and some other primate species scientists found they could deliver more genetic code while reducing the immune response. And the field started hunting for conditions that seemed a better match for gene therapy.

Zolgensma and Spark Therapeutics Luxturna, approved for government subsidy in March, both use the same adeno-associated virus to target cells that are easy to access and do not divide.

Luxturna treats a genetic cause of blindness by supplying a replacement copy of a defective gene to cells in the retina, allowing them to make a protein crucial for sight.

The gene is small and easy to package in the virus. And the eye, you can get at it relatively easy surgically, says Eye Research Australias Edwards. And [the retina] has immune-privilege the virus does not cause a widespread immune reaction.

Both Zolgensma and Luxturna are extraordinarily expensive, raising the question of whether gene therapy will be a medicine of the rich. Experts are hopeful that wont be the case.

Some of the early therapies will be for small groups, but eventually a gene therapy that can be used by many people will come online, says Professor Robyn Jamieson, head of the eye genetics research unit at the Childrens Medical Research Institute. Those economies of scale will push the price down for everyone.

And now the technology has been proven to work, competition among biotechs to develop new therapies is fierce. They are jaw-droppingly expensive now, says Rasko, but over time that competition should pull costs down.

And new facilities to make the viral machines at the heart of the treatment will also come online. This year NSW invested $25 million in a pilot factory to make viral vectors in Westmead.

None of this can come quickly enough for the hundreds of thousands of families across Australia living with genetic illnesses.

Shes very stubborn, very strong-willed, Adriana Baron says of her daughter, Mariana. And that helped her.Credit:Simon Schluter

To get Mariana the treatment she needed, Adriana had to battle first to get a diagnosis, then get approved for the treatment, and then get government funding to bring it into the country. But shes a fighter, just like her daughter.

Shes very stubborn, very strong-willed. And that helped her, says Adriana. If she wants to do things on her own, she tells you, I dont need any help, she does it herself.

Liam Mannixs Examine newsletter explains and analyses science with a rigorous focus on the evidence. Sign up to get it each week.

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A new era: After winding path and safety scares, gene therapy enters the clinic - Sydney Morning Herald

Our voice here is a moral voice – Martha’s Vineyard Times

The Marthas Vineyard Hebrew Center recently held a forum to discuss how to mitigate the fallout from the recently overturned Roe v. Wade decision by the Supreme Court, and to highlight the chief notion of the discourse advocacy for reproductive justice.

The Hebrew Center cares about this issue, and about pro choice, and abortion justice, began Rabbi Caryn Broitman, from a religious perspective.

Reaching far beyond the particulars of a decision to terminate a pregnancy, Broitman emphasized the need for women to be able to make their own choices concerning their own bodies, and stressed additional need to support the autonomy that comes with a person taking various socially and medically geared avenues.

The Hebrew Centers support for womens reproductive rights is not of political motivation, explained Broitman. Our voice here is a moral voice. It is a life voice. And its a spiritual, religious voice.

Broitman cited Israels ultra orthodox chief rabbi who said publicly in 1948 that theres no legal reason to prevent an abortion.

Jewish value of reproductive justice, said Broitman, is significant; for it is encompassed by the greater need to take care of ones body and ensure health and wellbeing. [Therefore,] women and pregnant people dont need to offer an excuse or reason to justify their abortion. Its our healthcare.

The Womens Centers, a leading organization for abortion care research work including stem cell research sees around 40,000 clients per year and has been a frequent target for anti-abortion terrorism, mainly as a response to its success in womens rights advocacy.

Elizabeth Barnes, former Chappy resident and president of the Womens Centers one of the largest abortioin providers nationwide spoke to the Hebrew Center crowd about her work. Barnes noted that current moment, women from Alabama and Tennessee where abortion has been deemed illegal have been provided access to the procedure through efforts by the organization to transport them to New Jerseys centers.

Barnes harkened back to her early days working for the cause, in a clinic in Pennsylvania, having started the job at the same time that two women, both of whom were her age, and also hailing from New England, were shot and killed in Brooklyn because of their association with a womens clinic.

Following the incident, Barnes said her family questioned her career path, expressing concerns over her safety; but Barnes could not be dissuaded because the work was too important.

Barnes made note that the shooting affirmed that importance, provoking women and supporters of reproductive justice to continue the efforts to maintain health equality. The directed violence, said Barnes, didnt work people persisted.

Barnes said through the evolution of the medicine of abortion, have, overtime, created an incredible community of brilliant thinkers who are saving peoples lives in complex abortion and materntity work, with the caveat of if given the opportunity.

Barnes relayed countless stories of women who have had to face numerous obstacles in their efforts to secure access to noninvasive medical abortions via oral pill, some traveling over 18 hours in order to terminate their five, six, or seven week pregnancy.

Some states, that have not banned abortion fully, still enact absurd waiting periods, in many cases resulting in doubling the amount of weeks a woman remains pregnant.

But, abortion is just part of the story, said Barnes, noting that Roe V. Wade was overturned in the midst of a nationwide diaper and baby formula shortage, further shedding light on the health access disparity women continuously endure.

The United States maternal mortality rate, Barnes said, is horrific, especially among women of color, and regardless of income.

Barnes said that despite abortion being legal in Massachusetts, theres a lot of progress yet to be made including on the Vineyard, which currently lacks access to even early, first trimester abortions. Barnes noted one particular instance, which left a few-weeks-pregnant woman who had already chosen to terminate, pregnant for longer, bringing with it all forms of distress. It begs the question of how a community can enhance its role as a womens health supporter, provider, and safe haven.

Marthas Vineyard is indeed a special place, said Barnes, but we are not special when advocating for abortion work. We need to get on it.

According to Talmudic texts written law and traditions of Judaism Broitman relayed that the essence of life is that which is after birth. Theres no question about it, she said.

Because of this understanding, it is the mothers life that takes precedence; not that of an unborn fetus. Life, explained Broitman, does not equate a fetus or potential life within a persons body to all of life.

Accentuating the traditional view of the importance of womens lives and health, Barnes offered a quote by well-known Rabbi Moses Sofer: No woman should have to save the world by destroying herself.

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Our voice here is a moral voice - Martha's Vineyard Times